Stannane, tributyl(1-ethoxyethenyl)- → 1-(3-(1-(Quinolin-6-yl)cyclopropyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone

HRID 1892407Notes

Reaction equation

HRID 1892407 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3([C:14]4[CH:15]=[C:16]5[C:21](=[CH:22][CH:23]=4)[N:20]=[CH:19][CH:18]=[CH:17]5)[CH2:13][CH2:12]3)=[N:9][N:10]=2)[N:7]=1.C([Sn](CCCC)(CCCC)[C:29]([O:31]CC)=[CH2:30])CCC>O1CCOCC1.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:20]1[C:21]2[C:16](=[CH:15][C:14]([C:11]3([C:8]4[N:6]5[N:7]=[C:2]([C:29](=[O:31])[CH3:30])[CH:3]=[CH:4][C:5]5=[N:10][N:9]=4)[CH2:13][CH2:12]3)=[CH:23][CH:22]=2)[CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 2

HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 581905686-(1-(6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)cyclopropyl)quinoline

Product 1

HCID 581905101-(3-(1-(Quinolin-6-yl)cyclopropyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-[1-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-cyclopropyl]-quinoline (30 mg, 0.093 mmol), PdCl2(PPh3)2 (6.5 mg, 0.0093 mmol) and tributyl(1-ethoxyvinyl)stannane (67 mg, 0.186 mmol) in 3 mL of 1,4-dioxane was heated at 90° C. for 3 h under nitrogen. The reaction mixture was diluted with EtOAc, washed with aqueous KF. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was dissolved in HOAc and 3 N HCl, and the solution was stirred at rt for 3 h. The solvent was removed under reduced pressure and the residue was dissolved in DCM, washed with saturated aqueous NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with EtOAc/MeOH gradient to afford the title compound as a yellow solid. 1H-NMR (400 MHz, CDCl3) 3 ppm 8.89 (dd, 1H), 8.13-8.04 (m, 3H), 7.93 (d, 1H), 7.87 (dd, 1H), 7.70 (d, 1H), 7.40 (dd, 1H), 2.51 (s, 3H), 1.92-1.89 (m, 2H), 1.73-1.69 (m, 2H). LCMS (method A): [MH]+=330, tR=4.18 min.

Workup

  1. washwashed with aqueous KF
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in HOAc
  6. customThe solvent was removed under reduced pressure
  7. dissolutionthe residue was dissolved in DCM
  8. washwashed with saturated aqueous NaHCO3 and brine
  9. dry with materialThe organic layer was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography on silica gel eluting with EtOAc/MeOH gradient

Sources & evidence

ORD record
ord-bcdeff7d364046259218a26d74f84e00
Source dataset
uspto-grants-2013_08
Patent number
US08507676B2

Reaction notes

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